The present study examined the expression of glucose‑regulated protein 78 (GRP78/Bip) in human pancreatic cancer cell lines and the effect of knockdown of GRP78 on the cleavage of poly (ADP-ribose) polymerase (PARP). Human pancreatic cancer cell lines (KP-2, MIAPaCa-2, Panc-1 and SUIT-2), constitutively expressed GRP78. We also demonstrated that ER stress induced by thapsigargin upregulated protein levels of GRP78. In the presence of thapsigargin, knockdown of GRP78 enhanced the PARP cleavage in the human pancreatic cancer cells. These results provide evidence that GRP78 is a potential therapeutic target for ‘difficult-to-treat’pancreatic cancer, in which ER stress signaling in part falls into disorder.